白细胞介素1β、白细胞介素1受体拮抗剂对癫痫大鼠行为、海马超微结构及NMDAR活性的影响  

Effect of interleukin-1 beta and interleukin-1 receptor antagonist on the behavior and hippocampal ultrastructure and activity of N-methyl-D-aspartate receptors in rats with seizure

作　　者：朱雨岚[1] 吴海威[1] 程莉晶[1] 孙威[1] 

机构地区：[1]哈尔滨医科大学第二临床医学院神经内科,黑龙江省哈尔滨市150086

出　　处：《中国临床康复》2005年第9期70-72,共3页Chinese Journal of Clinical Rehabilitation

基　　金：黑龙江省教育厅课题项目(10531121)~~

摘　　要：目的:探讨白细胞介素1β(IL-1β)及白细胞介素1受体拮抗剂(IL-1ra)对癫痫的影响,揭示癫痫发作的免疫学机制。方法:实验于2003-10/2004-06在哈尔滨医科大学第二临床医学院实验中心完成,侧脑室注射生理盐水,IL-1β及IL-1ra30min后戊四氮致痫观察大鼠行为,分别于致痫后2,8,24h处死大鼠,通过放射配基结合实验测定NMDA受体(NMDAR)活性,取海马CA3区电镜下观察超微结构的变化。结果:外源性IL-1β能够缩短癫痫发作的潜伏期,与生理盐水对照组相比差异有显著性意义(t=3.85,P<0.05),对癫痫发作强度的影响与对照组相比差异无显著性意义,观察到明显的神经元变性坏死,大鼠脑内NMDAR活性在致痫后个时间点均显著增强;IL-1ra对发作潜伏期的影响及发作强度的影响与对照组相比差异无显著性意义,但可明显减轻戊四氮致痫所导致的神经元损害,致痫大鼠脑内NMDAR活性各时间与对照组相比明显减低。结论:IL-1β通过提高NMDAR活性促进癫痫发生及发展,加重癫痫所导致的神经元损伤的程度,IL-1ra可以通过抑制IL-1β的活性,减轻其上述作用。AIM: To investigate the effect of interleukin- 1 beta(IL- 1β ) and interleukin- 1 receptor antagonist (IL- 1ra) on epilepsy, and unveil the immunologic mechanism of epilepsy.METHODS: The experiment was finished in the Laboratory Center of Second Clinical Medical College, Harbin Medical University, from October 2003 to June 2004. Thirty minute after injected into lateral ventricle with saline or IL- 1β or IL- 1ra, the rats were induced seizure by pentetrazole. The behavior of the rats with seizure was observed. The rats were killed at 2 hour, 8 hours and 24 hours, respectively. The activity of N- methyl- D- aspartate receptor(NMDAR)was detected with a radio- ligand binding assay. The ultrastructural in hippocampal CA3 of rats was observed under electron microscope.RESULTS: Exogenous application of IL- 1β could shorten the latent period of seizure; there was significant difference between the IL- 1β and saline groups(t=3.85,P< 0.05),but there was no significant difference as in the effect of IL- 1β on intensity of seizure between the two groups.The marked degeneration and necrosis of neurons was observed.The activity of NMDAR increased obviously after inducing seizure; In IL- 1ra group, there was no significant difference from the saline group in the latent period and intensity of seizure,but the injury of neuron caused by pentetrazole induced seizure was obviously lightened, and the activity of NMDAR was obviously decreased.CONCLUSION: IL- 1β can promote the onset and development of epilepsy by increasing the activity of NMDAR,and aggravate the degree of the seizure induced neuron injury.However,IL- 1ra can lighten the above- mentioned injury through inhibiting the activity of IL- 1β .

关 键 词：癫痫 白细胞介素1 受体 白细胞介素1/拮抗剂和抑制剂 受体 N-甲基-D-天冬氨酸 

分 类 号：R742.1[医药卫生—神经病学与精神病学]